Pharmaceutical industry transitioning to press-fit vial closures
If press-fit closures were the current standard for sealing pharmaceutical vials, would pharmaceutical companies switch to aluminum crimp caps?
Based on equivalent or superior performance data, and the simplification of the manufacturing process, the press-fit closure would be preferred over the crimp cap. Driven by data, pharma companies would not make the switch.
Conventional aluminum crimp caps
Traditional vial closure technology is a separate dual component system using aluminum crimp caps and stoppers. For liquid products the vials are stoppered with serum stoppers, which act as an interface to the drug product. The crimp caps are a metal over-seal that is crimped over the top of a stoppered vial.
For lyophilized (freeze-dried) products the filling systems partially seat lyo-stoppers inside the vial. This design provides minimal protection of the vial contents from particulates until the stoppers are fully seated inside the lyophilizer. Stoppers can also stick to the underside of the shelves in a lyo causing vials to fall or vials to remain unstoppered when they leave the lyo, which could leads to unit losses and operator interventions.
Within the filling process the crimps are applied only after the vials are stoppered and moved to a separate crimping station. This station is not within the filling isolator, resulting in a requirement for a large and complex machine. Separate chambers are mandatory for the crimp capping process to reduce the chance of metal particle generation, which can negatively affect drug product quality and patient safety. Particle generation can also be caused by the vibration of sortation bowls for stoppers.
The basics of press-fit closures
For the unfamiliar, it’s important to explain how a press-fit vial closure works.
Press-fit closures are made of plastic, and include two pieces—a cap with clips to hold the cap on to the vial neck, and a stopper. The cap comes pre-assembled from its manufacturer, in pre-sterilized or ready-to-sterilize options. A press-fit closure is applied by applying pressure to the cap until the clips click into place.
Press-fit caps reduce the risk of losing revenue due to incomplete crimp formation or loss of container integrity due to excessive seal forces.
An important thing to know is that the stopper is an industry-standard product. For example, Daikyo Saikyo’s PLASCAP press-fit closure comes with the popular D-777-1 stopper. ARaymondlife’s RayDyLyo press-fit closures use stoppers from several manufacturers.
Press-fit closures have been used successfully in the pharmaceutical market for several years. Approved drugs using press fit closures on the market today include Pfizer’s ACT-O-VIAL, Bayer’s BIO-SET, and Hospira’s ADD-vantage.
Manufacturing advantages of press-fit closures
Vanrx Aseptic Filling Workcells cap an entire nest of vials at once.
Using a press-fit closure reduces manufacturing complexity, as applying the cap and stopper do not require separate operations. With the increased regulatory focus on maintaining Grade A conditions through the completion of the capping process, the elimination of a separate crimping work centre offers significant cost savings and quality benefits.
For lyophilized products being processed with Vanrx’s Lyophilizer Loader Workcell, the nest of press-fit closures is placed on top of the vial nest before entering the lyophilizer. The cap holds the stopper off the vial allowing the use of standard serum stoppers. The ability to use serum stoppers reduces fragmentation in the clinic should the needle be inserted into the vial at the wrong angle.
After the vials are freeze dried, the closures are fully sealed by pressure applied from collapsing the lyophilizer’s shelves. Because the vials are completely and positively closed in the lyophilizer there is a reduction in the occurrence of “raised stoppers” and an improvement in headspace-gas control. All filling and closing operations are performed in Grade A space, reducing risk to the drug product. Vanrx’s partners in the Matrix Alliance have data showing significant improvements in lyophilization cycle times through the use of nested vials with press-fit closures, which still allow moisture to escape during the cycle.
Combinations of nested, pre-sterilized vials and nested, pre-sterilized press-fit closures are confirmed for compatibility through the Matrix Alliance. Partners in the Alliance have conducted testing on Vanrx aseptic filling machines, and then confirmed that their products are compatible. For example, Product Sets have been announced for SCHOTT adaptiQ vials and ARaymond RayDyLyo caps, Ompi Ez-fill vials and Daikyo PLASCAP closures, and SCHOTT adaptiQ and Daikyo PLASCAP.
Data is available, including container-closure integrity testing (CCIT), from the Matrix Alliance partner companies.
Marketing benefits of press-fit closures
Pharmaceutical marketers looking for a product differentiator should evaluate plastic press-fit vial closures. They can differentiate a product’s appearance. Colors can be customized, and for traceability a batch number or product name can be printed onto the body of the cap. For innovator companies, plastic snap caps can help differentiate the product against competition.
The differentiated closure is easy for clinicians to use. Also, there is no risk of ragged metal edges cutting through clinicians’ gloves.
The plastic snap caps are visibly different from commonly available aluminum crimp caps. To protect against tampering, once the cap has been flipped it is impossible to reposition it on top of the vial. The closures have tamper evident features that clearly show when it has been opened. Due to how the closure attaches to the vial, it is not possible to remove the cap without causing visible damage.
Would aluminum crimp caps be able to displace press-fit closures if they were the standard? Based on their improved performance and simplification of manufacturing processes, we would say ‘no.’
Go to the Matrix Alliance page and complete the form to request product and CCIT data.